The frequency of urination of healthy humans is generally 4-6 times a day and usually no urine is voided during sleep at night. The condition of an abnormally increased frequency of urination is called pollakiuria and the condition of involuntary emptying of the urinary bladder is known as urinary incontinence. Both morbidities are bothersome to the affected person because sleep is disturbed and going out is restricted. The frequency of occurring pollakiuria or urinary incontinence is particularly high in the bedridden aged persons and patients with dementia and there is a pressing need for development of useful therapeutic drug in this field, not only for patients and clinical doctors but also for the people taking charge of nursing care.
As therapeutic drugs designed to ameliorate pollakiuria and urinary incontinence through increase in bladder capacity, flavoxate, oxybutynin, propiverine and so on are used today.
Meanwhile, as pyrrole derivatives apparently resembling the compound of the present invention, the compounds listed below in Table 1 are known. However, none of them are known to have the first medicinal use, namely, to be useful for the treatment of disease such as pollakiuria or urinary incontinence.
TABLE 1 __________________________________________________________________________ Compound No. Structural formula Literature __________________________________________________________________________ R1 J. Prakt. Chem., 318, 663 (1976). - R2 J. Heterocyclic Chem., 14, 383 (1977), Z. Chem., 1, 349 (1961). - R3 J. Heterocyclic Chem., 14, 383 (1977). - R4 J. Heterocyclic Chem., 14, 383 (1977). - R5 Khim. Geterotsiki. Soedim., (9), 1217, (1975) (Chem. Abstr., 84, 59299 (1976)) - R6 J. Heterocyclic Chem., 14, 383 (1977). - R7 Khim. Geterotsiki. Soedim., (9), 1217, (1975) (Chem. Abstr., 84, 59299 (1976)) - R8 J. Pharm. Sci., 68, 317 (1979). - R9 Synthesis, 217 (1979). - R10 Synthesis, 55 (1974). - R11 J. Pharm. Sci., 65, 908 (1976). J. Heterocyclic Chem., 23, 397 (1986). - R12 Farmaco, Ed. Sc., 43, 103 (1988). - R13 Khim. Geterotsiki. Soedim., (9), 1217, (1975) (Chem. Abstr., 84, 59299 (1976)) - R14 J. Heterocyclic Chem., 14, 383 (1977). - R15 Khim. Geterotsiki. Soedim., (9), 1217, (1975) (Chem. Abstr., 84, 59299 (1976)) - R16 Farmaco, Ed. Sc., 43, 103 (1988). - R17 Farmaco, Ed. Sc., 43, 103, (1988). - R18 Farmaco, Ed. Sc., 43, 103 (1988). - R19 Farmaco, Ed. Sc., 43, 103 (1988). - R20 Farmaco, Ed. Sc., 43, 103 (1988). - R21 Farmaco, Ed. Sc., 43, 103 (1988). - R22 Farmaco, Ed. Sc., 43, 103 (1988). - R23 Farmaco, Ed. Sc., 43, 103 (1988). - R24 Farmaco, Ed. Sc., 43, 103 (1988). - R25 Farmaco, Ed. Sc., 43, 103 (1988). - R26 Farmaco, Ed. Sc., 43, 103 (1988). - R27 Farmaco, Ed. Sc., 43, 103 (1988). - R28 Farmaco, Ed. Sc., 43, 103 (1988). - R29 J. Chem. Res., Synop. (8), 266 (1992). J. Chem. Res., Miniprint, 2049 (1992). - R30 Heterocycles, 10, 261 (1978). - R31 Heterocycles, 10, 261 (1978). - R32 J. Org. Chem., 43, 4273 (1978). J. Chem. Soc., B, (1), 79 (1970). - R33 J. Org. Chem., 43, 4273 (1978). - R34 J. Org. Chem., 43, 4273 (1978). EP 358047 A2. - R35 J. Org. Chem., 43, 4273 (1978). - R36 J. Org. Chem., 43, 4273 (1978). - R37 J. Org. Chem., 43, 4273 (1978). Heterocycle s, 20, 829 (1983). - R38 J. Chem. Soc., B, (1), 79 (1970). - R39 Gazz. Chim. Ital., 71, 375 (1941). - R40 Justus Liebigs Ann. Chem., 447, 43 (1926). - R41 WO 93/19067. - R42 EP 480204 A1. - R43 EP 314009 A2. EP 389904 A2. - R44 Chem. Ber., 105, 1258 (1972). - R45 J. Org. Chem., 31, 4110 (1996). - R46 J. Org. Chem., 31, 4110 (1996). - R47 EP 389904 A2. - R48 EP 389904 A2. - R49 EP 389904 A2. __________________________________________________________________________